| Identification |
|---|
| HMDB Protein ID
| HMDBP14229 |
| Secondary Accession Numbers
| None |
| Name
| Genome polyprotein |
| Synonyms
|
Not Available
|
| Gene Name
| Not Available |
| Protein Type
| Unknown |
| Biological Properties |
|---|
| General Function
| Not Available |
| Specific Function
| Component of immature procapsids, which is cleaved into capsid proteins VP4 and VP2 after maturation (By similarity). Allows the capsid to remain inactive before the maturation step (By similarity).Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity). Capsid protein VP1 mainly forms the vertices of the capsid (By similarity). Capsid protein VP1, together with VP3, interacts with host cell sialic acids to provide virion attachment to target host cells (PubMed:26563423). This attachment induces virion internalization (PubMed:26563423). After binding to its receptor, the capsid undergoes conformational changes (By similarity). Capsid protein VP1 N-terminus (that contains an amphipathic alpha-helix) and capsid protein VP4 are externalized (By similarity). Together, they shape a pore in the host membrane through which viral genome is translocated to host cell cytoplasm (By similarity).Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity).Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity). Capsid protein VP3, together with VP1, interacts with host cell sialic acids to provide virion attachment to target host cells (PubMed:26563423).Lies on the inner surface of the capsid shell (By similarity). After binding to the host receptor, the capsid undergoes conformational changes (By similarity). Capsid protein VP4 is released, Capsid protein VP1 N-terminus is externalized, and together, they shape a pore in the host membrane through which the viral genome is translocated into the host cell cytoplasm (By similarity).Cysteine protease that cleaves viral polyprotein and specific host proteins (By similarity). It is responsible for the autocatalytic cleavage between the P1 and P2 regions, which is the first cleavage occurring in the polyprotein (By similarity). Cleaves also the host translation initiation factor EIF4G1, in order to shut down the capped cellular mRNA translation (By similarity). Inhibits the host nucleus-cytoplasm protein and RNA trafficking by cleaving host members of the nuclear pores (By similarity). Counteracts stress granule formation probably by antagonizing its assembly or promoting its dissassembly (PubMed:30867299).Plays an essential role in the virus replication cycle by acting as a viroporin. Creates a pore in the host reticulum endoplasmic and as a consequence releases Ca2+ in the cytoplasm of infected cell. In turn, high levels of cytoplasmic calcium may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication.Induces and associates with structural rearrangements of intracellular membranes. Displays RNA-binding, nucleotide binding and NTPase activities. May play a role in virion morphogenesis and viral RNA encapsidation by interacting with the capsid protein VP3.Localizes the viral replication complex to the surface of membranous vesicles. Together with protein 3CD binds the Cis-Active RNA Element (CRE) which is involved in RNA synthesis initiation. Acts as a cofactor to stimulate the activity of 3D polymerase, maybe through a nucleid acid chaperone activity.Localizes the viral replication complex to the surface of membranous vesicles (By similarity). It inhibits host cell endoplasmic reticulum-to-Golgi apparatus transport and causes the disassembly of the Golgi complex, possibly through GBF1 interaction (By similarity). This would result in depletion of MHC, trail receptors and IFN receptors at the host cell surface (By similarity). Plays an essential role in viral RNA replication by recruiting ACBD3 and PI4KB at the viral replication sites, thereby allowing the formation of the rearranged membranous structures where viral replication takes place (PubMed:31381608).Acts as a primer for viral RNA replication and remains covalently bound to viral genomic RNA. VPg is uridylylated prior to priming replication into VPg-pUpU (By similarity). The oriI viral genomic sequence may act as a template for this. The VPg-pUpU is then used as primer on the genomic RNA poly(A) by the RNA-dependent RNA polymerase to replicate the viral genome (By similarity). Following genome release from the infecting virion in the cytoplasm, the VPg-RNA linkage is probably removed by host TDP2 (By similarity). During the late stage of the replication cycle, host TDP2 is excluded from sites of viral RNA synthesis and encapsidation, allowing for the generation of progeny virions (By similarity).Involved in the viral replication complex and viral polypeptide maturation. It exhibits protease activity with a specificity and catalytic efficiency that is different from protease 3C. Protein 3CD lacks polymerase activity. Protein 3CD binds to the 5'UTR of the viral genome.Major viral protease that mediates proteolytic processing of the polyprotein (By similarity). Cleaves host EIF5B, contributing to host translation shutoff (By similarity). Cleaves also host PABPC1, contributing to host translation shutoff (By similarity). Binds and inhibits host IFIH1/MDA5, thereby inhibiting the type-I IFN production and the establishment of the antiviral state (PubMed:28424289). Cleaves host MAP3K7/TAK1, resulting in inhibition of TRAF6-triggered NF-kappa-B induction (PubMed:28424289). Cleaves host TICAM1; this interaction allows the virus to disrupt host TLR3 signaling (PubMed:24672048). Cleaves host IRF7, resulting in inhibition of type-I IFN production (PubMed:26608321). Cleaves host NLRP1, triggers host N-glycine-mediated degradation of the autoinhibitory NLRP1 N-terminal fragment (By similarity).Replicates the viral genomic RNA on the surface of intracellular membranes. May form linear arrays of subunits that propagate along a strong head-to-tail interaction called interface-I. Covalently attaches UMP to a tyrosine of VPg, which is used to prime RNA synthesis. The positive stranded RNA genome is first replicated at virus induced membranous vesicles, creating a dsRNA genomic replication form. This dsRNA is then used as template to synthesize positive stranded RNA genomes. ss(+)RNA genomes are either translated, replicated or encapsidated. |
| Pathways
|
Not Available
|
| Reactions
| Not Available |
| GO Classification
|
| Biological Process |
| viral RNA genome replication |
| suppression by virus of host toll-like receptor signaling pathway |
| suppression by virus of host NF-kappaB transcription factor activity |
| suppression by virus of host mRNA export from nucleus |
| suppression by virus of host MDA-5 activity |
| RNA-protein covalent cross-linking |
| pore-mediated entry of viral genome into host cell |
| endocytosis involved in viral entry into host cell |
| virion attachment to host cell |
| pore formation by virus in membrane of host cell |
| induction by virus of host autophagy |
| protein oligomerization |
| transcription, DNA-dependent |
| Cellular Component |
| host cell cytoplasmic vesicle membrane |
| host cell nucleus |
| integral to membrane of host cell |
| T=pseudo3 icosahedral viral capsid |
| membrane |
| Molecular Function |
| metal ion binding |
| cysteine-type endopeptidase activity |
| ion channel activity |
| RNA-directed RNA polymerase activity |
| structural molecule activity |
| nucleoside-triphosphatase activity |
| RNA helicase activity |
| RNA binding |
| ATP binding |
|
| Cellular Location
|
Not Available
|
| Gene Properties |
|---|
| Chromosome Location
| Not Available |
| Locus
| Not Available |
| SNPs
| Not Available |
| Gene Sequence
|
Not Available
|
| Protein Properties |
|---|
| Number of Residues
| Not Available |
| Molecular Weight
| 243797.645 |
| Theoretical pI
| Not Available |
| Pfam Domain Function
|
|
| Signals
|
Not Available
|
|
Transmembrane Regions
|
Not Available
|
| Protein Sequence
|
Not Available
|
| External Links |
|---|
| GenBank ID Protein
| Not Available |
| UniProtKB/Swiss-Prot ID
| Q68T42 |
| UniProtKB/Swiss-Prot Entry Name
| POLG_HED68 |
| PDB IDs
|
|
| GenBank Gene ID
| Not Available |
| GeneCard ID
| Not Available |
| GenAtlas ID
| Not Available |
| HGNC ID
| Not Available |
| References |
|---|
| General References
| - Xiang Z, Liu L, Lei X, Zhou Z, He B, Wang J: 3C Protease of Enterovirus D68 Inhibits Cellular Defense Mediated by Interferon Regulatory Factor 7. J Virol. 2015 Nov 25;90(3):1613-21. doi: 10.1128/JVI.02395-15. Print 2016 Feb 1. [PubMed:26608321 ]
- Oberste MS, Maher K, Schnurr D, Flemister MR, Lovchik JC, Peters H, Sessions W, Kirk C, Chatterjee N, Fuller S, Hanauer JM, Pallansch MA: Enterovirus 68 is associated with respiratory illness and shares biological features with both the enteroviruses and the rhinoviruses. J Gen Virol. 2004 Sep;85(Pt 9):2577-2584. doi: 10.1099/vir.0.79925-0. [PubMed:15302951 ]
- Xiang Z, Li L, Lei X, Zhou H, Zhou Z, He B, Wang J: Enterovirus 68 3C protease cleaves TRIF to attenuate antiviral responses mediated by Toll-like receptor 3. J Virol. 2014 Jun;88(12):6650-9. doi: 10.1128/JVI.03138-13. Epub 2014 Mar 26. [PubMed:24672048 ]
- Rui Y, Su J, Wang H, Chang J, Wang S, Zheng W, Cai Y, Wei W, Gordy JT, Markham R, Kong W, Zhang W, Yu XF: Disruption of MDA5-Mediated Innate Immune Responses by the 3C Proteins of Coxsackievirus A16, Coxsackievirus A6, and Enterovirus D68. J Virol. 2017 Jun 9;91(13). pii: JVI.00546-17. doi: 10.1128/JVI.00546-17. Print 2017 Jul 1. [PubMed:28424289 ]
- Liu Y, Sheng J, Baggen J, Meng G, Xiao C, Thibaut HJ, van Kuppeveld FJ, Rossmann MG: Sialic acid-dependent cell entry of human enterovirus D68. Nat Commun. 2015 Nov 13;6:8865. doi: 10.1038/ncomms9865. [PubMed:26563423 ]
- Liu Y, Sheng J, Fokine A, Meng G, Shin WH, Long F, Kuhn RJ, Kihara D, Rossmann MG: Structure and inhibition of EV-D68, a virus that causes respiratory illness in children. Science. 2015 Jan 2;347(6217):71-4. doi: 10.1126/science.1261962. [PubMed:25554786 ]
- Horova V, Lyoo H, Rozycki B, Chalupska D, Smola M, Humpolickova J, Strating JRPM, van Kuppeveld FJM, Boura E, Klima M: Convergent evolution in the mechanisms of ACBD3 recruitment to picornavirus replication sites. PLoS Pathog. 2019 Aug 5;15(8):e1007962. doi: 10.1371/journal.ppat.1007962. eCollection 2019 Aug. [PubMed:31381608 ]
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